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Biomedical subjects

J M Gutteridge

Publications and source records attributed to J M Gutteridge.

At least 145 records · Page 8Linked to original sources
PubMed1985

Catalase enhances damage to DNA by bleomycin-iron(II): the role of hydroxyl radicals.

Bleomycin degrades DNA under aerobic conditions when a ferrous salt is added. This reaction is enhanced by catalase and certain hydroxyl radical scavengers but inhibited by the addition of hydrogen peroxide. A ferricbleomycin complex is, however, stimulated by addition of hydrogen peroxide. These findings suggest that catalase removes hydrogen peroxide and in so doing prevents loss of ferrous ions and formation of hydroxyl radicals (OH.) by a Fenton-type reaction. It further suggests that OH. radicals, when formed, are more involved in the inactivation of bleomycin than in the release of thiobarbituric acid reactive material from DNA.

Animals↗
PubMed1985

Cerebral and ocular toxicity induced by desferrioxamine.

Seven patients with rheumatoid disease were given the iron-chelating drug desferrioxamine (DFX) to evaluate its possible anti-inflammatory effects. Two of these patients, who also received the anti-emetic prochlorperazine, lost consciousness for 48-72 h and then fully recovered. Electroencephalography showed abnormalities of the type associated with metabolic disturbance. One of these patients showed pyramidal features and subsequently developed an optic neuropathy and pigmentary retinopathy. Analysis of his cerebrospinal fluid showed a decrease in loosely-bound (catalytic) iron and increase in loosely-bound (catalytic) copper, total iron and products of lipid peroxidation, with values approaching normal as the symptoms resolved. Subsequent in vivo/vitro studies clearly demonstrated that the neurological effects were due to a synergistic action of desferrioxamine and prochlorperazine, probably resulting in exceptional fluxes of intra/extra cellular iron/copper disturbing noradrenergic and serotonergic systems. Two other patients who did not receive prochlorperazine, developed retinal problems which later improved, one after only 15 g of desferrioxamine. Our observations suggest a new model for metabolic encephalopathy studies and provide insight into the mechanisms of pigmentary retinopathy.

Adult↗
PubMed1984

Ferrous ion-EDTA-stimulated phospholipid peroxidation. A reaction changing from alkoxyl-radical- to hydroxyl-radical-dependent initiation.

The stimulatory effect of ferrous salts on the peroxidation of phospholipids can be enhanced by EDTA when the concentration of Fe2+ in the reaction is greater than that of EDTA. Hydroxyl-radical scavengers do not inhibit peroxidation until the concentrations of Fe2+ and EDTA in the reaction are equal. Lipid peroxidation is then substantially initiated by hydroxyl radicals derived from a Fenton-type reaction requiring hydrogen peroxide. Superoxide radicals appear to play some role in the formation of initiating species.

Chemical Phenomena↗
PubMed1984

Reactivity of hydroxyl and hydroxyl-like radicals discriminated by release of thiobarbituric acid-reactive material from deoxy sugars, nucleosides and benzoate.

Hydroxyl radicals (OH.) can be formed in aqueous solution by a superoxide (O2.-)-generating system in the presence of a ferric salt or in a reaction independent of O2.- by the direct addition of a ferrous salt. OH. damage was detected in the present work by the release of thiobarbituric acid-reactive material from deoxy sugars, nucleosides and benzoate. The carbohydrates deoxyribose, deoxygalactose and deoxyglucose were substantially degraded by the iron(II) salt and the iron(III) salt in the presence of an O2.- -generating system, whereas deoxyinosine, deoxyadenosine and benzoate were not. Addition of EDTA to the reaction systems producing radicals greatly enhanced damage to deoxyribose, deoxyinosine, deoxyadenosine and benzoate, but decreased damage to deoxygalactose and deoxyglucose. Further, OH. scavengers were effective inhibitors only when EDTA was present. Inhibition by catalase and desferrioxamine confirmed that H2O2 and iron salts were essential for these reactions. The results suggest that, in the absence of EDTA, iron ions bind to the carbohydrate detector molecules and bring about a site-specific reaction on the molecule. This reaction is poorly inhibited by most OH. scavengers, but is strongly inhibited by scavengers such as mannitol, glucose and thiourea, which can themselves bind iron ions, albeit weakly. In the presence of EDTA, however, iron is removed from these binding sites to produce OH. in 'free' solution. These can be readily intercepted by the addition of OH. scavengers.

Benzoates↗
PubMed1984

Streptonigrin-induced deoxyribose degradation: inhibition by superoxide dismutase, hydroxyl radical scavengers and iron chelators.

The aminoquinone antitumour antibiotic streptonigrin stimulates deoxyribose degradation in cell-free systems. This degradation is dependent both on reduction of the drug to a semiquinone and on traces of molecular oxygen in the reaction. Inhibition by a variety of hydroxyl radical scavengers and by catalase implicates a radical species with properties similar to the hydroxyl radical. Iron salts appear to play some part in radical formation as DETAPAC and desferrioxamine partly inhibit. Deoxyribose degradation under conditions of low oxygen concentration is strongly inhibited by superoxide dismutase.

Catalase↗
PubMed1984

Triglyceride-rich lipoproteins are responsible for thrombin generation induced by lipid peroxides.

Previous studies have shown that lipid peroxides promote thrombin generation in platelet-poor plasma. In the present study, it has been shown that triglyceride-rich lipoproteins, especially chylomicra of dietary origin, are responsible for this procoagulant activity. The generation of thrombin by lipid peroxides is also enhanced by their inhibitory action on antithrombin III. These results suggest a possible new relationship between dietary fat, lipid peroxidation and thrombus formation.

Antithrombin III↗
PubMed1984

Lipid peroxidation initiated by superoxide-dependent hydroxyl radicals using complexed iron and hydrogen peroxide.

Iron salts stimulate lipid peroxidation by decomposing lipid peroxides to produce alkoxyl and peroxyl radicals which initiate further oxidation. In aqueous solution ferrous salts produce OH. radicals, a reactive species able to abstract hydrogen atoms from unsaturated fatty acids, and so can initiate lipid peroxidation. When iron salts are added to lipids, containing variable amounts of lipid peroxide, the former reaction is favoured and OH. radicals contribute little to the observed rate of peroxidation. When iron is complexed with EDTA, however, lipid peroxide decomposition is prevented, but the complex reacts with hydrogen peroxide to form OH. radicals which are seen to initiate lipid peroxidation. Superoxide radicals appear to play an important part in reducing the iron complex.

Catalase↗
PubMed1984

Lipid peroxidation and possible hydroxyl radical formation stimulated by the self-reduction of a doxorubicin-iron (III) complex.

In the presence of ferric ions, doxorubicin forms a complex which self-reduces the iron moiety to form a ferrous complex. This ferrous complex can generate active radicals able to degrade deoxyribose as well as form a species greatly stimulatory towards lipid peroxidation. Both reactions may explain the damage to different sites within the body associated with doxorubicin therapy.

Animals↗
PubMed1984

Copper-phenanthroline-induced site-specific oxygen-radical damage to DNA. Detection of loosely bound trace copper in biological fluids.

Copper(II) ions, in the presence of 1,10-phenanthroline, O2 and a reducing agent, degrade DNA with the release of thiobarbituric-acid-reactive material. This reaction, dependent on the formation of oxygen radicals, was made the basis of a sensitive and specific assay for loosely bound copper in body fluids. When applied to certain extracellular fluids, trace amounts of copper could be detected in the lower micromolar range.

Binding Sites↗
PubMed1984

Mitomycin C-induced deoxyribose degradation inhibited by superoxide dismutase. A reaction involving iron, hydroxyl and semiquinone radicals.

Mitomycin C stimulates deoxyribose degradation with the release of thiobarbituric acid-reactive material under conditions of low oxygen concentration. This damage is inhibited by scavengers of the hydroxyl radical, iron chelators and the specific proteins catalase and superoxide dismutase. The reactive radical species appears to arise from a Fenton-type sequence in which iron is reduced by the mitomycin C semiquinone radical.

Animals↗
PubMed1984

Inhibition by the protein ceruloplasmin of lipid peroxidation stimulated by an Fe3+-ADP-adriamycin complex.

Self-reduction of an Fe3+-ADP-adriamycin complex under anaerobic conditions and reduction of ferricytochrome c by the complex under aerobic conditions were strongly inhibited by ceruloplasmin, but not by superoxide dismutase or albumin at the same protein concentration. Ceruloplasmin, a protein with ferroxidase activity, is able to catalyse oxidation of Fe2+ to the ferric state. The inhibitory activity of ceruloplasmin towards reactions stimulated by the complex suggests that Fe2+ is formed during the self-reduction process. As expected, the Fe3+-ADP-adriamycin complex stimulated lipid peroxidation in which the Fe2+ moiety was implicated. This stimulation was again effectively prevented by ceruloplasmin but not by superoxide dismutase.

Adenosine Diphosphate↗